crossing96/oncoscreening huggingface dataset:
Regulation of TLR4-induced IL-6 response in bladder cancer cells by opposing actions of MAPK and PI3K signaling.	PURPOSE: Toll-like receptor 4 (TLR4) was found to be aberrantly expressed in bladder cancer, inducing some genes expression and facilitating tumor progression. Recent data suggest that tumor associated Interleukin-6 (IL-6) correlates with tumor size and grade in bladder cancer. However, the molecule mechanisms of the induction of IL-6 response in bladder cancer cells are not well elucidated. In this study, we manage to find out whether TLR4 signaling is involved in the production of IL-6 by human bladder cancer cells, and the detailed molecule mechanisms by which IL-6 is up-regulated. METHODS: We selected human bladder cancer T24 cell line in the present study, and examined its expression of TLR4 and CD14 by using flow cytometry. TLR4 signaling was activated by lipopolysaccharide (LPS) and IL-6 secretion in culture supernatants was tested by using ELISA kit. The expression of p38, ERK, JNK and Akt were determined by western-blot analysis using specific antibodies. RESULTS: Our study demonstrated that CD14 and TLR4 were constitutively expressed in T24 cells and activation of TLR4 signaling by LPS resulted in phosphorylation of MAPK and PI3K pathways and up-regulation of IL-6 in dose- and time-dependent manner. Pretreatment of cells with SB203580 (inhibitor of p38) and PD98059 (inhibitor of ERK) attenuated LPS-induced IL-6 expression, whereas LY294002 (inhibitor of PI3K) markedly amplified the LPS-stimulated synthesis of IL-6. CONCLUSIONS: Our results demonstrate that activation of TLR4 signaling in bladder cancer cells induces tumor-associated IL-6 expression via activation of p38 and ERK, whereas activation of PI3K/Akt exerts an opposing action.	bladder
Differences in shotgun protein expression profile between superficial bladder transitional cell carcinoma and normal urothelium.	This study was undertaken to identify differences in protein expression profiles between superficial bladder transitional cell carcinoma (BTCC) and normal urothelial cells. We used laser capture microdissection (LCM) to harvest purified cells, and used two-dimensional liquid chromatography (2D-LC) followed by electrospray ionization-tandem mass spectrometry (ESI-MS/MS) to separate and identify the peptide mixture. A total of 440/438 proteins commonly appeared in 4 paired specimens. Multi-step bioinformatic procedures were used for the analysis of identified proteins; 175/179 of the 293/287 proteins that were specific expressed in tumor/normal cells own gene ontology (GO) biological process annotation. Compared with the entire list of the international protein index (IPI), there are 52/46 GO terms exhibited as enriched and 6/10 exhibited as depleted, respectively. Significantly altered pathways between tumor and normal cells mainly include oxidative phosphorylation, focal adhesion, etc. Finally, descriptive statistics show that the shotgun proteomics strategy has practice directive significance for biomarker discovery by two-dimensional electrophoresis (2-DE) technology.	bladder
Polymorphisms of methylenetetrahydrofolate reductase and methionine synthase genes and bladder cancer risk: a case-control study with meta-analysis.	Folate deficiency due to the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) variants leads to carcinogenesis by affecting DNA synthesis, repair, and methylation. We hypothesized that the MTHFR C677T, A1298C, and MS A2756G polymorphisms are associated with risk of bladder cancer. In a case-control study of 239 bladder cancer cases and 250 cancer-free controls, we found that the MTHFR 677TT genotype was statistically significantly associated with an increased risk of bladder cancer compared with the 677CC genotype (OR = 2.06, 95% CI = 1.16-3.64). Furthermore, the TA haplotype was associated with a significantly increased bladder cancer risk (OR = 1.38, 95% CI = 1.05-1.81) than was the most common haplotype, CA (e.g., CA denotes MTHFR 677C -1298A). We also found that the combined genotypes with 4-6 variant (risk) alleles (i.e., MTHFR 677T, 1298A, and MS 2756G alleles) were associated with an increased risk of bladder cancer (OR = 1.62, 95% CI = 1.03-2.53) compared with those with 0-3 variants, and this increased risk was more pronounced among subgroup of older people (OR = 1.71, 95% CI = 1.03-2.83). A meta-analysis of seven studies did not show a significant risk of bladder cancer in the MTHFR polymorphisms. The MTHFR polymorphisms and their haplotypes appear to jointly contribute to risk of bladder cancer.	bladder
Characterization of intron-1 haplotypes of the G protein beta 4 subunit gene--association with survival and progression in patients with urothelial bladder carcinoma.	PURPOSE: Polymorphisms in genes encoding subunits of heterotrimeric G proteins have been repeatedly associated with various cancers. As G beta gamma signaling is presumed to be involved in proliferation and invasion processes, we analyzed genetic variations in regulatory regions of GNB4, which encodes the G beta 4 subunit, for their potential influence on cancer progression. EXPERIMENTAL DESIGN: We characterized the promoter of GNB4 and screened the promoter as well as exon 1 and intron 1 for single nucleotide polymorphisms by sequencing 100 healthy controls. Following a haplotype analysis, we determined the functional impact upon gene expression of the defined haplotypes by reporter assays, electrophoretic mobility shift assay and western blot. In addition, these haplotypes were tested for their relation to the disease course of urothelial bladder cancer. RESULTS: Whereas the promoter of GNB4 revealed no polymorphisms, 33 single nucleotide polymorphisms located in exon 1 and intron 1 were identified and together with a common exon-4 polymorphism implemented in haplotype analysis, which resulted in the determination of distinct haplotype blocks. Reporter activity was haplotype-dependently different (P=0.001). 1*1/1*1 showed increased G beta 4 protein (P=0.003), and bladder cancer patients carrying this diplotype displayed more progressive disease (P=0.046) and a significantly increased mortality (P=0.046). In multivariate analysis,the diplotypes were independent prognostic factors for survival and progression. CONCLUSION: Intron-1 haplotypes of GNB4 may, thus, serve as predictive markers for progression and survival of patients suffering from bladder cancer.	bladder
Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection.	BACKGROUND: Chromosome missegregation and the resulting aneuploidy is a common change in neoplasia. The Aurora kinase A (AURKA) gene, which encodes a key regulator of mitosis, is frequently amplified and/or overexpressed in cancer cells, and the level of AURKA amplification is associated with the level of aneuploidy. We examined whether AURKA gene amplification is a biomarker for the detection of bladder cancer. METHODS: The effect of ectopic expression of Aurora kinase A (AURKA) using an adenoviral vector in simian virus 40-immortalized urothelial cells (SV-HUC) on centrosome multiplication and chromosome copy number was measured in vitro by immunofluorescence and fluorescence in situ hybridization (FISH), respectively. The FISH test was also used to examine AURKA gene copy number in exfoliated cells in voided urine samples from 23 patients with bladder cancer and 7 healthy control subjects (training set), generating a model for bladder cancer detection that was subsequently validated in an independent set of voided urine samples from 100 bladder cancer patients and 148 control subjects (92 healthy individuals and 56 patients with benign urologic disorders). An AURKA gene score (the proportion of cells with three or more AURKA signals) was used to produce receiver operating characteristic (ROC) curves and to calculate the specificity and sensitivity of the AURKA FISH test. Differences between mean AURKA scores in different pathogenetic groups of bladder cancer stratified according to histological grade and stage were tested by unpaired Mann-Whitney t tests or one-way Wilcoxon tests. All statistical tests were two-sided. RESULTS: Forced overexpression of AURKA in urothelial cells induced amplification of centrosomes, chromosome missegregation, and aneuploidy, and natural overexpression was detectable in in situ lesions from patients with bladder cancer. The FISH test for the AURKA gene copy number performed on the validation set yielded a specificity of 96.6% (95% confidence interval [CI] = 92.3% to 98.5%) and sensitivity of 87% (95% CI = 79.0% to 92.2%) and an area under the ROC curve of 0.939 (95% CI = 0.906 to 0.971; P < .001). CONCLUSION: Overexpression of AURKA can cause aneuploidy in urothelial cells, and the AURKA gene copy number is a promising biomarker for detection of bladder cancer.	bladder
Quantitative risk stratification and individual comprehensive therapy for invasive bladder cancers in China.	BACKGROUND: To evaluate the risk factors for invasive bladder cancer and to develop a predictive model for the improvement of individual comprehensive therapy for invasive bladder cancers. MATERIALS AND METHODS: The records of 356 patients with invasive bladder cancer, operated on at three Chinese medical institutes, were reviewed. The Cox proportional hazards regression model was used to assess the clinical and pathological variables affecting disease-free survival (DFS). The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). PI was used to categorize the patients into different risk groups. Kaplan-Meier survival curves followed with log-rank test were plotted to compare the difference. RESULTS: Tumor configuration (RR = 1.60, P = 0.01), multiplicity (RR = 1.41, P = 0.04), histological subtype (RR = 2.13, P < 0.01), tumor stage (RR = 2.50, P < 0.01), tumor grade (RR = 2.35, P < 0.01), node status (RR = 2.48, P < 0.01), and neoadjuvant chemotherapy (RR = 0.46, P = 0.02), had independent prognostic significance for DFS. PI = 0.47 x (configuration) + 0.34 x (multiplicity) + 0.76 x (tumor histological subtype) + 0.92 x (stage) + 0.86 x (grade) + 0.91 x (node status) - 0.79 x (neoadjuvant chemotherapy). The range of PI was -0.32 to 6.52, which was equally divided into three risk groups with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.01). Meanwhile, the patient's probability of survival could be calculated by PI. CONCLUSIONS: Seven factors (tumor configuration, multiplicity, histological subtype, tumor stage, tumor grade, node status, neoadjuvant chemotherapy) affect the prognosis after radical cystectomy (RC) for invasive bladder cancer. PI can be used to optimize the individual comprehensive therapy. Given fewer perioperative complications, fast recovery from surgery and relatively satisfactory quality of life, ureterocutaneostomy, and ileal conduit are suitable for the patients with short expected life spans.	bladder
Voiding symptoms and urodynamic findings in patients with modified ileal neobladde.	The aim of our study was to find the cause of urinary incontinence and voiding dysfunction in patients undergoing radical cystectomy and orthotopic bladder replacement with modified ileal neobladder (Reddy). Twenty-eight incontinent patients (operated on between 1988 and 2004) were involved in our examination. Based on the complaints of the patients, continence status was evaluated and divided into two groups: group I: partially incontinent (only night-time incontinence) n = 11 (39.3%) and group II: totally incontinent (night-time and daytime incontinence) n = 17 (60.7%). Detailed urodynamic examination (enterocystometry and urethral pressure profile) in addition to involuntary neobladder contractions and capacity detection were carried out on all patients. Furthermore resting pressure and maximal voluntary contraction ability of the sphincter were determined and statistically analyzed in both groups. Significant difference was noticed in resting pressure and maximal voluntary contraction ability of the sphincter among the partially incontinent and totally incontinent patients. Frequency, intensity and duration of involuntary neobladder contractions also showed significant differences between the two groups. Incontinence of neobladder depends not only on the destruction of resting and contraction capability of the urethral sphincter, but also on the presence or absence of involuntary contractions in the wall of the neobladder and decreased capacity of the neobladder.	bladder
Plasmacytoid urothelial carcinoma of the bladder: histological and clinical features of 5 cases.	PURPOSE: Urothelial carcinoma with plasmacytoid morphology is a rare and only recently described histological variant. To date only 22 cases have been published. We present clinical and histopathological features of 5 cases of plasmacytoid urothelial carcinoma at our institutions. MATERIALS AND METHODS: From a consecutive series of 130 muscle invasive urothelial carcinoma cases 3 of plasmacytoid urothelial carcinoma (2.3%) were identified. Two additional plasmacytoid urothelial carcinoma cases, including 1 that was noninvasive, were also studied. Data were collected from clinical charts, histological review and followup. RESULTS: Four patients had a muscle invasive tumor at first presentation. The nonmuscle invasive plasmacytoid urothelial carcinoma represents the second published case in the literature. Conventionally differentiated urothelial carcinoma was focally present in every case. Plasmacytoid urothelial carcinoma cells were dyshesive and showed abundant eosinophilic cytoplasm, leading to a plasmacytoid appearance. Positive staining for epithelial markers confirmed the epithelial nature of the tumor. All tumors showed negative E-cadherin expression. Adjuvant or neoadjuvant chemotherapy seemed to have a beneficial effect on survival in patients with advanced tumors since they experienced prolonged survival. CONCLUSIONS: Plasmacytoid urothelial carcinoma is a rare variant of urothelial carcinoma with defined clinical and pathological characteristics. Diagnostic pitfalls are missing hematuria and no grossly identifiable tumor despite muscle invasive tumor stage. Cases only show mucosal induration and thickened bladder walls. Our data raise the possibility that the loss of E-cadherin expression is a prerequisite for plasmacytoid urothelial carcinoma. Awareness of these aspects should lead to earlier diagnosis and improved long-time survival in patients with plasmacytoid urothelial carcinoma.	bladder
Signaling pathway for TNF-alpha-induced MMP-9 expression: mediation through p38 MAP kinase, and inhibition by anti-cancer molecule magnolol in human urinary bladder cancer 5637 cells.	We investigated the molecular mechanisms involved in the expression of matrix metalloproteinase-9 (MMP-9) and the inhibition of MMP expression by magnolol in 5637 human urinary bladder cancer cells. Tumor necrosis factor-alpha (TNF-alpha) stimulated the secretion of MMP-9 in 5637 cells, as shown by zymography and promoter assay. The transcription factor nuclear factor kappaB (NF-kappaB) binding site was identified by gel-shift assay to be a cis-element for TNF-alpha activation of the MMP-9 promoter. Our results also demonstrated that TNF-alpha stimulates MMP-9 expression via the p38 MAP kinase signaling pathway in 5637 cells. Moreover, p38 MAP kinase-mediated MMP-9 gene regulation in response to TNF-alpha is involved in the NF-kappaB response element in 5637 cells. In addition, magnolol inhibited TNF-alpha-induced expression of the MMP-9, as determined by zymography and immunoblot, in 5637 cells. The TNF-alpha-induced invasion and migration of cells was inhibited by magnolol, as assessed by a modified boyden chamber and wound-healing assays, respectively. Finally, magnolol blocked MMP-9 expression, at least in part, by decreasing the binding of transcription factor NF-kappaB to DNA. In conclusion, TNF-alpha induced MMP-9 expression in 5637 cells by activating the transcription factor NF-kappaB, which is involved in the p38 MAP kinase-mediated control of MMP-9 regulation. Magnolol inhibited MMP-9 expression through the transcription factor NF-kappaB in TNF-alpha-induced 5637 cells.	bladder
Immunohistochemistry of p63 in primary and secondary vulvar Paget's disease.	Vulvar Paget's disease (VPD) is classified into primary and secondary types. Differentiation of these subsets in biopsy specimen is important for appropriate therapy. Expression profile of cytokeratin (CK) 7 and CK20, gross cystic disease fluid protein-15 and uroplakin III has been reported as a differentiation marker of primary and secondary VPD. To examine the role of p63 immunostaining in differential diagnosis between primary VPD and VPD secondary to urothelial carcinoma (VPD-UC), expression of p63 was examined in nine cases of VPD. Paget cells in seven cases of VPD without UC did not express p63. In two cases of VPD associated with UC, Paget cells and UC cells had identical CK expression profile. UC cells were positive for p63 in both cases. In one case, Paget cells were positive for p63 and examination of the resected specimen showed that VPD was secondary to UC. In another case, Paget cells were negative for p63 and this was diagnosed as primary VPD independent of UC. This indicates that p63 is absent in Paget cells in primary VPD and is therefore useful in differentiating primary VPD from VPD-UC.	bladder
Linitis plastica of the rectum secondary to bladder carcinoma: a report of two cases and its MR features.	Rectal linitis plastica (RLP) is a circumferentially infiltrating intramural anaplastic carcinoma that results in a rigid constricted rectum with thickened walls. A long delay between the onset of symptoms and the diagnosis often occurs because RLP can mimic a lot of diseases and endoscopy and biopsies are often negative, owing to the fact that the mucosa is frequently unaffected in RLP. RLP secondary to bladder cancer is rarely described in the English literature. We present the first report of the MR features of secondary rectal linitis plastica from a bladder carcinoma. Two patients presented with changed bowel habits. All diagnostic tests were inconclusive. In both patients, pelvic T(2) weighted MR images revealed a double-layered thickening of the rectal wall with an inner isointense circumferential thickening of the submucosa and outer hypointense circumferential thickening of the muscular rectal wall. Based on MRI, further investigations were performed and secondary RLP was diagnosed. It is important to establish the diagnosis of RLP early because of its bad prognosis. The value of MRI in supporting the diagnosis of RLP should not be underestimated. As endoscopy plus biopsy can often be negative, we suggest that, if pelvic MRI shows a concentric double layered thickening of the rectal wall over a long segment, then the diagnosis of RLP should be considered. This should prompt further investigations either to confirm or rule out the diagnosis of RLP by performing endoscopy with deep rectal wall biopsies.	bladder
[Severe cystitis and perivesical collection posterior to Mitomycin C immediate instillation in a patient with inadverted bladder perforation].	We present the clinical case of a 40 years male patient who, after a TURBt for non-muscle invasive recurrence with inadverted vesical perforation and Mitomycin C immediate instillation, come in his fourth postoperative day to the emergency room with severe irritative urinary symptomatology. An ultrasound was indicated, documenting a perivesical collection. The management was conservative with vesical drilling for 10 days and a puncture/drainage was necessary to solve it.	bladder
Low-level arsenic exposure in drinking water and bladder cancer: a review and meta-analysis.	Although exposure to high levels of arsenic in drinking water is associated with excess cancer risk (e.g., skin, bladder, and lung), lower exposures (e.g., <100-200 microg/L) generally are not. Lack of significant associations at lower exposures may be attributed to methodologic issues (e.g., inadequate statistical power, exposure misclassification), or to differences in the dose-response relationship at high versus low exposures. The objectives of this review and meta-analysis were to evaluate associations, examine heterogeneity across studies, address study design and sample size issues, and improve the precision of estimates. Eight studies of bladder cancer and low-level arsenic exposure met our inclusion criteria. Meta-analyses of never smokers produced summary relative risk estimates (SRREs) below 1.0 (highest versus lowest exposure). The SRRE for never and ever smokers combined was elevated slightly, but not significantly (1.11; 95% CI: 0.95-1.30). The SRRE was somewhat elevated among ever smokers (1.24; 95% CI: 0.99-1.56), and statistical significance was observed in some subgroup analyses; however, heterogeneity across studies was commonly present. Although uncertainties remain, low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer. More studies with detailed smoking history will help resolve whether smoking is an effect modifier.	bladder
Alpha-fetoprotein-producing transitional cell carcinoma of the urinary bladder: a case report.	We report a 76-year-old man with alpha-fetoprotein (AFP)-producing transitional cell carcinoma of the bladder. Although the serum level of AFP was 1,428 ng/ml, and he was anti-hepatitis C virus (anti-HCV) antibody-positive, liver tumors were not detected by either a computed tomography (CT) scan or a hepatic angiography. However, removal of a bladder tumor by transurethral resection and subsequent pathological examination revealed a grade III transitional cell carcinoma (TCC). Furthermore, immunohistochemical detection of AFP was diffuse-positive. After the tumor partially responded to concomitant chemoradiotherapy, the serum AFP levels decreased to 966 ng/ml. However, the tumor eventually progressed with multiple lung metastases, and serum AFP levels increased to 3,906 ng/ml. In conclusion, AFP-producing TCC of urinary bladder is rare, and the nature and pathophysiology remains unclear and warrants further investigation.	bladder
A meta-analysis on XRCC1 R399Q and R194W polymorphisms, smoking and bladder cancer risk.	To elucidate the role of X-ray repair cross-complementing group 1 (XRCC1) R399Q and R194W genotypes in bladder cancer risk, all available studies were considered in the present meta-analysis, with 4152 patients and 5372 controls for R399Q and 3215 patients and 4313 controls for R194W. Studies were identified in PubMed up to June 2008. Overall, the 399Q allele showed no significant effect on bladder cancer compared to 399R allele in all subjects. Insignificant association between R399Q and bladder cancer was observed under other genetic contrasts in worldwide population, Caucasians and never-smokers. Among ever-smokers, protective effects of 399QQ genotype were observed under recessive model [P = 0.004, fixed-effects (FEs) model odds ratio (OR) = 0.65; 95% confidence interval (CI) (0.49, 0.86), I(2) = 0% P(heterogeneity) = 0.57] and homozygote contrast (P = 0.01, FE OR = 0.66; 95% CI (0.49, 0.90), I(2) = 0%, P(heterogeneity) = 0.76). No apparent effect of 194W allele compared to 194R on bladder cancer risk was found in all subjects and Caucasians. It indicated that XRCC1 R399Q and R194W might not be risk factors to bladder cancer, but the 399QQ genotype decreased susceptibility of bladder cancer under recessive model and homozygote contrast among ever-smokers. Further studies based on larger, stratified population were required to explore the role of XRCC1 polymorphisms in bladder cancer risk.	bladder